The Leiden University Medical Centre research group led by Prof. Martine Jager, members of UM Cure 2020 consortium, published last month the results of two original research projects.
Dr. Niels Brouwer, PhD student at the Department of Ophthalmology of Leiden University Medical Centre, is the first author of two papers published last month on Cancers journal. The group led by Prof. Martine Jager, used tissue from enucleated uveal melanoma (UM) patients for assessing the association between known UM genetic events and two biological processes, ischaemia and angiogenesis.
Earlier studies showed that some genetic events in the uveal melanoma cells are associated with a higher risk of spreading to other parts of the body - metastization. The most described genetic predictors are monosomy of chromosome 3, gain of chromosome 8q and loss of BRCA1-associated protein 1 (BAP1) expression.
On the first paper, the authors studied angiogenesis, which is the ability of the tumour to produce new blood vessels, increasing nutrients and oxygen supply and the probability of metastasize. This study demonstrates that tumours with monosomy 3 and BAP1-loss have more new vessels than those without these alterations.
The second paper is about ischaemia, which means shortage of oxygen supply from the blood in the tumour tissue. An important mediator is hypoxia inducible factor 1-alpha (HIF1a), which is increased in ischemic conditions and activates angiogenesis to ultimately regain oxygen with more blood arriving the tumour through new blood vessels. High HIF1a expression is related to cell proliferation and angiogenesis. Again, monosomy 3 and BAP1-loss were associated with an increased expression of HIF1a.
These two studies unravelled biological processes involved in the UM metastization process and its association genetic alterations. Further studies are needed to translate these findings into clinical implications, however, these biological processes might be future targets of anti-tumoral treatments to be tested in metastatic UM patients.